Clinico-Biochemical Profile and Identification of Independent Risk Factors of Frequent Relapse in Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Background and aim Nephrotic syndrome is one of the commonest glomerular diseases in children, and the majority of them have minimal change lesions in histology with a favorable outcome. Most children with minimal change disease (MCD) are steroid-sensitive, but half of them have a frequent relapse and a prolonged course. This study was conducted to evaluate the clinical manifestations and biochemical profile and to determine independent risk factors of frequent relapse in children with steroid-sensitive nephrotic syndrome (SSNS). Methods This was a tertiary care hospital-based observational study conducted at the pediatric department of Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from October 2017 to September 2019. Fifty-three children from age one to 15 years admitted with steroid-sensitive nephrotic syndrome diagnosed as per the International Study of Kidney Disease in Children (ISKDC) criteria were enrolled in the study. On admission, history-taking, physical examination, and routine hematological and biochemical tests were carried out. Children who had no infection were started oral prednisolone at the dose of 2 mg/kg/day for six weeks, followed by 1.5 mg/kg/day on alternate days for six weeks with daily follow-up for evidence of proteinuria till remission. The parameters evaluated were age at presentation, sex, type of presentation, precipitating factors, laboratory findings, and rapidity of steroid response. All children were followed up for one year, and those with no relapse over a period of one year after remission served as the control group to determine the risk factors for relapse. Data were analyzed using standard statistical software (Stata version 13.1, StataCorp LLC, College Station, Texas, USA). Results Of the 53 cases, 47% of the children had a relapse. In the relapse category, 88% were male, and 67% were between one and 5.5 years. The clinical manifestations during the first episode in the relapse group were similar to the no relapse group. Investigations revealed that 64% of the children with relapse had serum total protein ≤ 4.2 g/dL (p = 0) and that 59% had serum albumin ≤ 1.8 g/dL (p = 0.004). In the relapse group, 41% of the children went into remission within two weeks of initiation of therapy as compared with 80% in the no relapse group. Conclusion The risk factors determined for relapse in SSNS are male sex, younger age, low serum albumin, low serum total protein, and delayed response to steroid therapy.

Chromosome 1p31.1 Deletion Syndrome: Limited Expression.

Chromosomal microdeletion syndromes usually present with neurological abnormalities, developmental delays, and various systemic abnormalities. 1p31 microdeletion syndrome is one of the novel microdeletion syndromes that usually presents with developmental delay, intellectual disability, various craniofacial abnormalities, and other systemic abnormalities in a proportion of cases. NEGR1 and NFIA are few of the genes present in this locus responsible for these symptoms. However, none of the reported cases had only isolated intellectual disability. Here, we are reporting a case of 1p31 microdeletion syndrome with isolated moderate intellectual disability and hyperactivity in an 11-year-old boy. It is essential for clinicians to be aware of such an atypical presentation of 1p31.1 microdeletion syndrome, to maintain reasonable clinical suspicion in cases with unexplained intellectual disability.

Diabetes mellitus in an adolescent girl with intellectual disability caused by novel single base pair duplication in the PTRH2 gene: Expanding the clinical spectrum of IMNEPD.

BACKGROUND: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is an extremely rare autosomal recessive disorder with variable expressivity, caused by biallelic mutations in the PTRH2 gene. Core features are global developmental delay or isolated speech delay, intellectual disability, sensorineural hearing loss, ataxia, and pancreatic insufficiency (both exocrine and endocrine). Additional features may include postnatal microcephaly, peripheral neuropathy, facial dysmorphism, and cerebellar atrophy. In literature, there are only a few anecdotal case reports and none of the previous cases presented with diabetic ketoacidosis. METHODS: We are reporting a 12-year old adolescent girl with mild intellectual disability who presented with fever, pain abdomen for 2 days, and fast breathing for one day. RESULTS: Her random blood sugar was 472 mg/dl and arterial blood gas revealed high anion gap metabolic acidosis. Urine examination showed ketonuria. On further evaluation, she was found to have demyelinating sensorimotor polyneuropathy and sensorineural hearing loss. Neuroimaging and other ancillary investigations were normal. Whole exome sequencing revealed a novel homozygous single base pair duplication in exon 1 of the PTRH2 gene (c.127dupA, p.Ser43LysfsTer11), confirming the diagnosis of IMNEPD. CONCLUSIONS: Apart from describing a novel single base pair duplication causing protein truncation in the PTRH2 gene for the first time, our case also expanded the clinical spectrum of IMNEPD, as this is the first case with seemingly pure neurodevelopmental phenotype, who later developed diabetes mellitus, without any exocrine pancreatic abnormality. IMNEPD should be considered in children or adolescents with global developmental delay or intellectual disability when they develop diabetes mellitus.

Pancytopenia without Hepatosplenomegaly: A Rare Manifestation of Extrapulmonary Tuberculosis in an Adolescent Boy.

Extrapulmonary tuberculosis (TB) is a well-recognized cause of pyrexia of unknown origin. However, clinical presentation of TB in children with isolated hematological abnormalities is extremely rare. Anemia, usually normocytic, normochromic, leukopenia, leukocytosis, thrombocytopenia, thrombocytosis, and monocytosis are more common complications of TB rather than pancytopenia. Only anecdotal case reports and small case series are available in this regard. We are reporting an 18-year-old boy who presented with on and off low-grade fever for 3 months and anorexia and progressive pallor for 1 month. After extensive workup, pancytopenia remained unexplained. Bone marrow (BM) examination revealed caseating granulomas, along with Mantoux positivity and contact with sputum-positive pulmonary TB. He responded favorably to antitubercular therapy (ATT) within 2 months. This report alerts clinicians to be vigilant regarding the rare possibility of BM TB while investigating unexplained pancytopenia, as it is completely reversible with ATT.